Elise A. Chong, MD, discusses real-world liso-cel efficacy and safety, outpatient use, and future directions in relapsed/refractory mantle cell lymphoma.
In the analysis, the overall response rate (ORR) among patients who received liso-cel (n = 121) was 89% (95% CI, 82%-94%), and the complete response (CR) rate was 79% (95% CI, 71%-86%), compared with 83% and 72%, respectively, in the phase 1 TRANSCEND-NHL-001 trial (NCT02631044) which supported the
Cytokine release syndrome (CRS) occurred in 65% of patients, and immune effector cell–associated neurotoxicity syndrome (ICANS) occurred in 36%. The 6-month nonrelapse mortality (NRM) rate was 2% (95% CI, 0%-5.5%).
"I'd say that preliminarily, the 6-month real-world data look very consistent with what we've seen in the [TRANSCEND] clinical trial. This analysis just provides added support with these real-world data that [liso-cel] remains an important option for patients with relapsed/refractory MCL," Chong said in an exclusive interview with OncLive® at the
In the interview, Chong discussed the unmet need in Bruton tyrosine kinase (BTK) inhibitor–refractory MCL, efficacy and safety findings presented at the conference, and future priorities.
Elise A. Chong, MD, is an assistant professor of medicine at the Hospital of the University of Pennsylvania and a physician at the Abramson Cancer Center at Penn Medicine in Philadelphia.
Chong: Liso-cel is a CD19-directed CAR [chimeric antigen receptor] T-cell therapy that’s approved for [relapsed/refractory MCL] after 2 prior lines of therapy, including a BTK inhibitor.1 When we look at [MCL] that is refractory specifically to BTK inhibitors, these [MCLs] tend to be aggressive, and we have limited effective treatment options in that setting. That’s one of the reasons why CAR T-cell therapies and [liso-cel] are such important options for these patients.
The main reason these data are important is that the real-world data for liso-cel are limited. In fact, there are none, because [liso-cel] was recently approved in the United States in May 2024.[Liso-cel] wasn’t
In terms of efficacy, the [ORR] was 89%, and the CR rate was 79%, which is in line with what we saw in the pivotal TRANSCEND [MCL] trial that was the basis for the approval. The median follow-up is 6 months, which is a little bit short, but preliminarily, the data look consistent with what has been previously published based on the original clinical trial. [The] 6-month [PFS, DOR, and OS] [were] all reported. [DOR] was 81% at 6 months, PFS was 79% at 6 months, and [OS] was 92% at 6 months.
Safety also mimicked what we saw from the [TRANSCEND MCL] trial. In terms of [CRS], we saw about 65% of patients had [CRS] of all grades. Only 2 of those events were grade 4, the rest were grades 1 and 2. There were no deaths from CRS. [In terms of] ICANS, [we] saw about 36% of patients experience ICANS, 14% of those were grade 3 or higher. [Another item of note] was that the 6-month NRM rate was only 2%. [These NRM data were] encouraging, although obviously we need longer-term data. Finally, 39% of patients were treated in the outpatient setting. Looking at how those patients did specifically, about 60% of them were hospitalized, and there were no deaths, which is also noteworthy.
The major issue, at least when we look at the CAR T-cell therapy products, like [brexucabtagene autoleucel (Tecartus; brexu-cel)], for example, that have longer-term data, is that these responses don’t appear to be durable when we look at further follow-up. We still need approaches in the [relapsed/refractory] setting [for] more durable therapies. There’s a lot of movement in MCL to try to get away from chemotherapy. Whether that movement may be CAR T-cell therapies or combination therapies that either involve bispecific antibodies, lenalidomide [Revlimid], or a BTK inhibitor, there’s a lot of promise for whether we can use some of these combinations more effectively to improve durable first-line treatments so that we’re not maybe having to deal with these relapses as soon.
Finally, we need to do a better job of risk-stratifying and defining what high-risk MCL is. There are lots of ways we define [high-risk MCL], it’s pretty inconsistent, and outcomes on clinical trials are different depending upon how high risk the population of patients enrolled truly was. I don’t think that [MCL] is one-size-fits-all, and selecting therapies that are appropriately intense or less intense for different flavors of [MCL] may help optimize treatment in the future.
Editor’s Note: This transcript has been edited for grammar and clarity using artificial intelligence tools.
